1. Field of the Invention
The invention generally relates to novel compositions and methods for targeted delivery of a membrane permeable drug to cells by temporarily rendering it membrane impermeable. In particular, the invention provides conjugates comprising a membrane permeable drug linked to a moiety that is not membrane permeable, thereby preventing the drug from entering cells. Light exposure either i) cleaves the linkage, allowing the drug to enter the cells or ii) allows the conjugate to enter the cell, wherein the linkage is cleaved and the drug is released.
2. Background of the Invention
A major challenge of drug delivery is insuring bioavailability. Usually, drugs must be water soluble, and hence hydrophilic, in order to be successfully administered in vivo. At the same time, in order to reach a targeted location of action, the drug must usually enter and/or cross biological membranes, which requires the drug to have hydrophobic properties. Balancing these two opposing requirements is a major challenge when designing drug delivery methods.
A further challenge in drug delivery is the achievement of controlled, targeted delivery. Many drugs are administered systemically in a form that does not allow medical professionals to control when or where the drug will be active. As a result, unwanted, toxic side effects can occur. For example, drugs used for cancer treatment non-selectively attack rapidly dividing cells of all types, not just cancer cells, and usually cause severe side effects in recipients.
There is a need in the art to develop new compositions and methods for controlled, targeted delivery of drugs.